Stroke Update: What Happens Next


These new studies describe events and risks that go after, or before, the onset of symptoms.



Ten modifiable risk factors are responsible for 90% of strokes worldwide and hypertension leads the way, accounting for almost half of strokes, according to the National Stroke Association.   

To increase awareness about stroke and its prevention, May was designated National Stroke Awareness Month.

Five new stroke studies describe the latest developments in stroke care and prevention.

Extended window for thrombolysis after stroke

Thrombolysis guided by perfusion imaging is safe and effective up to 9 hours after the onset of stroke, according to Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) trial investigators.

Among patients in the multicenter, randomized, placebo-controlled trial who had ischemic stroke and salvageable brain tissue, there were more with no or minor neurologic deficits with the use of alteplase between 4.5 and 9.0 hours after stroke onset or at the time they awoke with stroke symptoms than with the use of placebo. The alteplase group had more cases of symptomatic cerebral hemorrhage.

The results were published online on May 9, 2019, in the New England Journal of Medicine.

The primary outcome-a score of 0 or 1 on the modified Rankin scale; range, 0 (no symptoms) to 6 (death) at 90 days-occurred in 35.4% and 29.5% of the patients in the alteplase and placebo groups, respectively. Symptomatic intracerebral hemorrhage occurred in 6.2% of the patients in the alteplase group vs 0.9% (1 patient) in the placebo group. No significant between-group difference in functional improvement was seen at 90 days.

The study authors noted that the time to initiate intravenous thrombolysis for acute ischemic stroke is generally limited to within 4.5 hours after the onset of symptoms but that some trials have suggested the treatment window may be extended.

Increased hemorrhage risk after aspirin

Preventive, low-dose aspirin increases the risk of intracranial hemorrhage in patients who do not have symptomatic cardiovascular disease, and intensive blood pressure reduction decreases the risk of hematoma expansion in patients who have deep intracerebral hemorrhage (ICH).

Both findings were reported online on May 13, 2019 in JAMA Neurology.

In a systematic review and meta-analysis, the main outcomes for aspirin vs control were any intracranial hemorrhage, intracerebral hemorrhage, subdural or extradural hemorrhage, and subarachnoid hemorrhage.

Low-dose aspirin was associated with an increased risk of any intracranial bleeding. The relative risk increase was greatest for subdural or extradural hemorrhage and less for intracerebral hemorrhage and subarachnoid hemorrhage.

Intracerebral hemorrhage risk was heightened for persons of Asian race/ethnicity and those with a low body mass index.

The authors suggested that the use of low-dose aspirin for the primary prevention of cardiovascular events remains controversial because the increased risk of bleeding may offset the overall benefit.

Reduced blood pressure leads to reduced hematoma expansion risk

The association of intensive blood pressure reduction with a decreased risk of hematoma expansion in deep ICH was not associated with improved outcomes.

Trial participants were randomized to intensive treatment (systolic blood pressure [SBP] target, 110– 139 mmHg) or standard treatment (SBP target, 140–179 mmHg). The main outcome, hematoma expansion, was defined as an increase greater than 33% in hematoma volume between baseline and 24 hours. Functional outcome was evaluated with the modified Rankin Scale 90 days after the ICH.

Intensive treatment was associated with a decreased risk of hematoma expansion, and the association was modified by the specific deep location of the ICH. There was a reduction in risk of hematoma expansion with intensive vs standard treatment among basal ganglia ICH but not thalamic ICH. Intensive treatment was not associated with an improvement in the modified Rankin Scale score distribution.

The authors noted that hypertension is the strongest risk factor for spontaneous ICH that involves deep brain regions but whether intensive blood pressure reduction in the acute care setting decreases hematoma expansion or improves outcomes in patients with deep ICH appears to be unknown.

Increased recurrent stroke risk after TIA and minor stroke

Diffusion-weighted imaging (DWI) positivity is associated with an increased long-term risk of recurrent stroke after transient ischemic attack (TIA) and minor stroke.

Consecutive patients who had TIA or minor stroke (NIH Stroke Scale [NIHSS] ≤3) in the population-based Oxford Vascular Study underwent brain MRI at baseline and stroke risk on 10-year follow-up was stratified.

Of patients who had TIA or minor stroke, 24% had acute lesions on DWI. A positive DWI was associated with an increased 10-year risk of recurrent ischemic stroke after an index TIA or a stroke with NIHSS 0–1 but not after a stroke with NIHSS 2–3. Ischemic stroke risk after DWI-positive TIA was at least equivalent to that after DWI-negative stroke. DWI positivity was most predictive of 10-year risk after cryptogenic events.

The authors suggested that the findings, reported online on April 17, 2019 in Neurology, support a tissue-based definition of minor stroke as well as TIA.

Fracture risk goes up after ischemic stroke

The risk of low trauma fracture goes up by more than 30% after ischemic stroke, but existing fracture risk scores do not account for history of stroke as a high-risk condition, according to study authors.

Now the Fracture Risk after Ischemic Stroke (FRAC-Stroke) score may help clinicians identify ischemic stroke survivors at higher risk for low-trauma fracture within 1 year of hospital discharge.

The results were published online on May 13, 2019 in JAMA Neurology.

The FRAC-Stroke score was derived in 20 435 patients from the Ontario Stroke Registry who were hospitalized for ischemic stroke. Low-trauma fracture occurred within 1 year of discharge in 3.6% of patients in the derivation cohort, where age; discharge modified Rankin score (mRS); and history of rheumatoid arthritis, osteoporosis, falls, and previous fracture were associated with the cumulative incidence of low trauma fracture.

Model discrimination in the validation cohort was good. Discharge mRS was an important discriminator of risk, which was highest in patients with mRS 3 and 4 and lowest in bedbound patients (mRS 5). From the lowest to the highest FRAC-Stroke quintile, the cumulative incidence of 1-year low-trauma fracture increased from 1.3% to 9.0% in the validation cohort.

The authors noted that risk predictions in the FRAC-Stroke score can be used to select patients for bone densitometry screening or, for high-risk patients, consideration for empirical bisphosphonate therapy.


1. May is National Stroke Awareness Month [press release]. Centennial, CO: National Stroke Association. Accessed May 17, 2019.

2. Ma H, Campbell BC, Parsons MW, et al, for the EXTEND Investigators. Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke.N Engl J Med. 2019 May 9;380:1795-1803. doi: 10.1056/NEJMoa1813046.

3. Huang WY, Saver JL, Wu YL, et al. Frequency of intracranial hemorrhage with low-dose aspirin in individuals without symptomatic cardiovascular disease: a systematic review and meta-analysis.JAMA Neurol. 2019 May 13. doi: 10.1001/jamaneurol.2019.1120. [Epub ahead of print]

4. Leasure AC, Qureshi AI, Murthy SB, et al. Association of intensive blood pressure reduction with risk of hematoma expansion in patients with deep intracerebral hemorrhage.JAMA Neurol. 2019 May 13. doi: 10.1001/jamaneurol.2019.1141. [Epub ahead of print]

5. Hurford R, Li L, Lovett N, et al. Prognostic value of “tissue-based” definitions of TIA and minor stroke: population-based study.Neurology. 2019 Apr 17. pii: 10.1212/WNL.0000000000007531. doi: 10.1212/WNL.0000000000007531. [Epub ahead of print]

6. Smith EE, Fang J, Alibhai SM, et al. Derivation and external validation of a scoring system for predicting fracture risk after ischemic stroke in a Canadian cohort.JAMA Neurol. 2019 May 13. doi: 10.1001/jamaneurol.2019.1114. [Epub ahead of print]

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